CA2203745A1 - Enzyme de conversion pro-proteinique - Google Patents

Enzyme de conversion pro-proteinique

Info

Publication number: CA2203745A1
Authority: CA; Canada
Prior art keywords: human; renin; prorenin; cells; protein
Prior art date: 1996-07-26
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002203745A

Other languages

English (en)

Inventor

Robert Day

Nabil G. Seidah

Remi Martel

Michel Chretien

Tim Reudelhuber

Guy Leclerc

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Institut de Recherches Cliniques de Montreal IRCM

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-07-26

Filing date

1997-04-25

Publication date

1998-01-26

1997-04-25 Application filed by Individual filed Critical Individual

1997-07-25 Priority to JP50834398A priority Critical patent/JP2001505870A/ja

1997-07-25 Priority to US09/214,555 priority patent/US6380171B1/en

1997-07-25 Priority to EP97932685A priority patent/EP0920494A2/fr

1997-07-25 Priority to PCT/CA1997/000535 priority patent/WO1998004686A2/fr

1997-07-25 Priority to AU36170/97A priority patent/AU3617097A/en

1997-07-25 Priority to CA 2259129 priority patent/CA2259129A1/fr

1998-01-26 Publication of CA2203745A1 publication Critical patent/CA2203745A1/fr

Status Abandoned legal-status Critical Current

Links

102000004190 Enzymes Human genes 0.000 title claims description 28
108090000790 Enzymes Proteins 0.000 title claims description 28
210000004027 cell Anatomy 0.000 claims abstract description 34
102000004169 proteins and genes Human genes 0.000 claims abstract description 21
108090000623 proteins and genes Proteins 0.000 claims abstract description 20
108091034117 Oligonucleotide Proteins 0.000 claims abstract description 19
230000014509 gene expression Effects 0.000 claims abstract description 14
102000012210 Proprotein Convertase 5 Human genes 0.000 claims abstract description 13
108010022052 Proprotein Convertase 5 Proteins 0.000 claims abstract description 12
208000037803 restenosis Diseases 0.000 claims abstract description 9
230000030279 gene silencing Effects 0.000 claims abstract description 7
230000002265 prevention Effects 0.000 claims abstract 2
238000000034 method Methods 0.000 claims description 21
230000002401 inhibitory effect Effects 0.000 claims description 8
239000002243 precursor Substances 0.000 claims description 7
230000004663 cell proliferation Effects 0.000 claims description 6
150000007523 nucleic acids Chemical class 0.000 claims description 6
239000002773 nucleotide Substances 0.000 claims description 6
125000003729 nucleotide group Chemical group 0.000 claims description 6
230000000694 effects Effects 0.000 claims description 5
108020004707 nucleic acids Proteins 0.000 claims description 4
102000039446 nucleic acids Human genes 0.000 claims description 4
210000000663 muscle cell Anatomy 0.000 claims description 3
230000000295 complement effect Effects 0.000 claims 3
108091028043 Nucleic acid sequence Proteins 0.000 claims 2
FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
125000003275 alpha amino acid group Chemical group 0.000 claims 1
108090000783 Renin Proteins 0.000 abstract description 93
101001072081 Homo sapiens Proprotein convertase subtilisin/kexin type 5 Proteins 0.000 abstract description 44
102100028255 Renin Human genes 0.000 abstract description 43
210000001519 tissue Anatomy 0.000 abstract description 32
239000002299 complementary DNA Substances 0.000 abstract description 24
230000000692 anti-sense effect Effects 0.000 abstract description 17
210000004739 secretory vesicle Anatomy 0.000 abstract description 15
210000004100 adrenal gland Anatomy 0.000 abstract description 14
239000013604 expression vector Substances 0.000 abstract description 13
210000003734 kidney Anatomy 0.000 abstract description 13
108020004999 messenger RNA Proteins 0.000 abstract description 12
210000004404 adrenal cortex Anatomy 0.000 abstract description 11
150000001413 amino acids Chemical class 0.000 abstract description 11
239000003102 growth factor Substances 0.000 abstract description 10
230000036454 renin-angiotensin system Effects 0.000 abstract description 10
230000004913 activation Effects 0.000 abstract description 9
230000001919 adrenal effect Effects 0.000 abstract description 9
230000035755 proliferation Effects 0.000 abstract description 8
210000000329 smooth muscle myocyte Anatomy 0.000 abstract description 8
210000003368 zona glomerulosa Anatomy 0.000 abstract description 8
238000012761 co-transfection Methods 0.000 abstract description 7
210000002826 placenta Anatomy 0.000 abstract description 7
238000012360 testing method Methods 0.000 abstract description 6
208000027418 Wounds and injury Diseases 0.000 abstract description 4
239000000074 antisense oligonucleotide Substances 0.000 abstract description 4
238000012230 antisense oligonucleotides Methods 0.000 abstract description 4
210000004556 brain Anatomy 0.000 abstract description 4
230000028327 secretion Effects 0.000 abstract description 4
208000006170 carotid stenosis Diseases 0.000 abstract description 3
230000006378 damage Effects 0.000 abstract description 3
230000001419 dependent effect Effects 0.000 abstract description 3
210000002216 heart Anatomy 0.000 abstract description 3
208000014674 injury Diseases 0.000 abstract description 3
210000001550 testis Anatomy 0.000 abstract description 3
230000009471 action Effects 0.000 abstract description 2
230000003143 atherosclerotic effect Effects 0.000 abstract description 2
210000004204 blood vessel Anatomy 0.000 abstract description 2
201000010099 disease Diseases 0.000 abstract description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
238000003364 immunohistochemistry Methods 0.000 abstract description 2
210000004072 lung Anatomy 0.000 abstract description 2
210000000496 pancreas Anatomy 0.000 abstract description 2
230000002062 proliferating effect Effects 0.000 abstract description 2
210000002027 skeletal muscle Anatomy 0.000 abstract description 2
210000000813 small intestine Anatomy 0.000 abstract description 2
210000002784 stomach Anatomy 0.000 abstract description 2
210000001685 thyroid gland Anatomy 0.000 abstract description 2
210000004185 liver Anatomy 0.000 abstract 1
229940088598 enzyme Drugs 0.000 description 22
108091032973 (ribonucleotides)n+m Proteins 0.000 description 18
235000018102 proteins Nutrition 0.000 description 13
101500027983 Rattus norvegicus Octadecaneuropeptide Proteins 0.000 description 12
229940046166 oligodeoxynucleotide Drugs 0.000 description 12
239000000523 sample Substances 0.000 description 12
241000699666 Mus <mouse, genus> Species 0.000 description 11
102000006437 Proprotein Convertases Human genes 0.000 description 11
108010044159 Proprotein Convertases Proteins 0.000 description 11
238000003776 cleavage reaction Methods 0.000 description 11
230000007017 scission Effects 0.000 description 11
238000001890 transfection Methods 0.000 description 11
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
101001072057 Mus musculus Proprotein convertase subtilisin/kexin type 5 Proteins 0.000 description 9
241000283973 Oryctolagus cuniculus Species 0.000 description 9
235000001014 amino acid Nutrition 0.000 description 9
108010076504 Protein Sorting Signals Proteins 0.000 description 8
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 8
239000012634 fragment Substances 0.000 description 8
210000002460 smooth muscle Anatomy 0.000 description 8
238000001727 in vivo Methods 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
108010026579 prorenin processing enzyme Proteins 0.000 description 7
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
241000700159 Rattus Species 0.000 description 6
238000009826 distribution Methods 0.000 description 6
230000003169 placental effect Effects 0.000 description 6
238000010186 staining Methods 0.000 description 6
241000282412 Homo Species 0.000 description 5
238000010240 RT-PCR analysis Methods 0.000 description 5
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
238000009396 hybridization Methods 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
210000000217 JG cell Anatomy 0.000 description 4
208000031481 Pathologic Constriction Diseases 0.000 description 4
230000003213 activating effect Effects 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
235000012000 cholesterol Nutrition 0.000 description 4
238000010790 dilution Methods 0.000 description 4
239000012895 dilution Substances 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
230000008569 process Effects 0.000 description 4
238000012545 processing Methods 0.000 description 4
230000036262 stenosis Effects 0.000 description 4
208000037804 stenosis Diseases 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 3
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 3
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 3
238000013459 approach Methods 0.000 description 3
238000003556 assay Methods 0.000 description 3
210000001715 carotid artery Anatomy 0.000 description 3
238000010367 cloning Methods 0.000 description 3
238000010276 construction Methods 0.000 description 3
230000003247 decreasing effect Effects 0.000 description 3
238000011534 incubation Methods 0.000 description 3
238000002372 labelling Methods 0.000 description 3
230000003902 lesion Effects 0.000 description 3
239000002609 medium Substances 0.000 description 3
235000011164 potassium chloride Nutrition 0.000 description 3
239000001103 potassium chloride Substances 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
230000002797 proteolythic effect Effects 0.000 description 3
230000001105 regulatory effect Effects 0.000 description 3
108091008146 restriction endonucleases Proteins 0.000 description 3
238000012216 screening Methods 0.000 description 3
239000000758 substrate Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
210000001235 zona fasciculata Anatomy 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 2
PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 2
PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 2
102000008873 Angiotensin II receptor Human genes 0.000 description 2
108050000824 Angiotensin II receptor Proteins 0.000 description 2
101800000733 Angiotensin-2 Proteins 0.000 description 2
102400000345 Angiotensin-2 Human genes 0.000 description 2
108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
108020004635 Complementary DNA Proteins 0.000 description 2
108020004414 DNA Proteins 0.000 description 2
102000004961 Furin Human genes 0.000 description 2
108090001126 Furin Proteins 0.000 description 2
WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
101000579218 Homo sapiens Renin Proteins 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
101100033674 Mus musculus Ren2 gene Proteins 0.000 description 2
101710135898 Myc proto-oncogene protein Proteins 0.000 description 2
102100038895 Myc proto-oncogene protein Human genes 0.000 description 2
238000000636 Northern blotting Methods 0.000 description 2
208000031074 Reinjury Diseases 0.000 description 2
241000283984 Rodentia Species 0.000 description 2
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
101710150448 Transcriptional regulator Myc Proteins 0.000 description 2
102000009618 Transforming Growth Factors Human genes 0.000 description 2
108010009583 Transforming Growth Factors Proteins 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
229960002478 aldosterone Drugs 0.000 description 2
229950006323 angiotensin ii Drugs 0.000 description 2
210000004899 c-terminal region Anatomy 0.000 description 2
239000002775 capsule Substances 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
230000008045 co-localization Effects 0.000 description 2
230000021615 conjugation Effects 0.000 description 2
210000004351 coronary vessel Anatomy 0.000 description 2
230000007423 decrease Effects 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000012744 immunostaining Methods 0.000 description 2
239000000463 material Substances 0.000 description 2
230000035800 maturation Effects 0.000 description 2
108010023815 mouse propeptide convertase 5 Proteins 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
210000001672 ovary Anatomy 0.000 description 2
239000002245 particle Substances 0.000 description 2
230000001817 pituitary effect Effects 0.000 description 2
239000013600 plasmid vector Substances 0.000 description 2
238000012340 reverse transcriptase PCR Methods 0.000 description 2
229910052709 silver Inorganic materials 0.000 description 2
239000004332 silver Substances 0.000 description 2
239000007787 solid Substances 0.000 description 2
241000894007 species Species 0.000 description 2
210000004377 supraoptic nucleus Anatomy 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
239000013598 vector Substances 0.000 description 2
102000004881 Angiotensinogen Human genes 0.000 description 1
108090001067 Angiotensinogen Proteins 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
239000011547 Bouin solution Substances 0.000 description 1
108090000712 Cathepsin B Proteins 0.000 description 1
102000004225 Cathepsin B Human genes 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
108020004394 Complementary RNA Proteins 0.000 description 1
108091035707 Consensus sequence Proteins 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
238000001712 DNA sequencing Methods 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
238000009007 Diagnostic Kit Methods 0.000 description 1
241000283074 Equus asinus Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
229910017974 NH40H Inorganic materials 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
239000000020 Nitrocellulose Substances 0.000 description 1
108091005461 Nucleic proteins Proteins 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
241000283977 Oryctolagus Species 0.000 description 1
-1 PC1 Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102000003992 Peroxidases Human genes 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
101001098832 Rattus norvegicus Proprotein convertase subtilisin/kexin type 5 Proteins 0.000 description 1
102000013275 Somatomedins Human genes 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
108010006785 Taq Polymerase Proteins 0.000 description 1
SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
208000015234 adrenal cortex adenoma Diseases 0.000 description 1
210000001943 adrenal medulla Anatomy 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
208000014594 aldosterone-producing adenoma with seizures and neurological abnormalities Diseases 0.000 description 1
238000010171 animal model Methods 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
239000012503 blood component Substances 0.000 description 1
230000037198 cardiovascular physiology Effects 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
210000004252 chorionic villi Anatomy 0.000 description 1
230000004186 co-expression Effects 0.000 description 1
239000003184 complementary RNA Substances 0.000 description 1
239000000306 component Substances 0.000 description 1
238000007887 coronary angioplasty Methods 0.000 description 1
230000001054 cortical effect Effects 0.000 description 1
239000012228 culture supernatant Substances 0.000 description 1
210000004748 cultured cell Anatomy 0.000 description 1
RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
230000002950 deficient Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
238000002405 diagnostic procedure Methods 0.000 description 1
238000010586 diagram Methods 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
210000002889 endothelial cell Anatomy 0.000 description 1
230000003511 endothelial effect Effects 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
238000005194 fractionation Methods 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
239000010931 gold Substances 0.000 description 1
239000000122 growth hormone Substances 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
206010020718 hyperplasia Diseases 0.000 description 1
230000002055 immunohistochemical effect Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000002955 isolation Methods 0.000 description 1
229960003299 ketamine Drugs 0.000 description 1
230000002132 lysosomal effect Effects 0.000 description 1
210000003712 lysosome Anatomy 0.000 description 1
230000001868 lysosomic effect Effects 0.000 description 1
210000003794 male germ cell Anatomy 0.000 description 1
230000028161 membrane depolarization Effects 0.000 description 1
210000003716 mesoderm Anatomy 0.000 description 1
DWCZIOOZPIDHAB-UHFFFAOYSA-L methyl green Chemical compound [Cl-].[Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC(=CC=1)[N+](C)(C)C)=C1C=CC(=[N+](C)C)C=C1 DWCZIOOZPIDHAB-UHFFFAOYSA-L 0.000 description 1
238000013508 migration Methods 0.000 description 1
230000005012 migration Effects 0.000 description 1
230000017095 negative regulation of cell growth Effects 0.000 description 1
230000008692 neointimal formation Effects 0.000 description 1
238000007857 nested PCR Methods 0.000 description 1
208000029986 neuroepithelioma Diseases 0.000 description 1
238000011587 new zealand white rabbit Methods 0.000 description 1
229920001220 nitrocellulos Polymers 0.000 description 1
210000003463 organelle Anatomy 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000007310 pathophysiology Effects 0.000 description 1
108040007629 peroxidase activity proteins Proteins 0.000 description 1
210000003635 pituitary gland Anatomy 0.000 description 1
239000013612 plasmid Substances 0.000 description 1
230000008488 polyadenylation Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
230000020978 protein processing Effects 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
238000000746 purification Methods 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
230000000580 secretagogue effect Effects 0.000 description 1
238000010532 solid phase synthesis reaction Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
230000009261 transgenic effect Effects 0.000 description 1
238000011824 transgenic rat model Methods 0.000 description 1
230000003827 upregulation Effects 0.000 description 1
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
230000002227 vasoactive effect Effects 0.000 description 1
238000001262 western blot Methods 0.000 description 1
BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
229960001600 xylazine Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6454—Dibasic site splicing serine proteases, e.g. kexin (3.4.21.61); furin (3.4.21.75) and other proprotein convertases
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Zoology (AREA)
Wood Science & Technology (AREA)
Organic Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Microbiology (AREA)
Medicinal Chemistry (AREA)
Biochemistry (AREA)
General Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)

CA002203745A 1996-07-26 1997-04-25 Enzyme de conversion pro-proteinique Abandoned CA2203745A1 (fr)

Priority Applications (6)

Application Number	Priority Date	Filing Date	Title
JP50834398A JP2001505870A (ja)	1996-07-26	1997-07-25	プロタンパク質変換酵素
US09/214,555 US6380171B1 (en)	1996-07-26	1997-07-25	Pro-protein converting enzyme
EP97932685A EP0920494A2 (fr)	1996-07-26	1997-07-25	Enzyme de conversion de preproteines
PCT/CA1997/000535 WO1998004686A2 (fr)	1996-07-26	1997-07-25	Enzyme de conversion de preproteines
AU36170/97A AU3617097A (en)	1996-07-26	1997-07-25	Pro-protein converting enzyme
CA 2259129 CA2259129A1 (fr)	1996-07-26	1997-07-25	Enzyme de conversion de preproteines

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US2100896P	1996-07-26	1996-07-26
US60/021,008		1996-07-26

Publications (1)

Publication Number	Publication Date
CA2203745A1 true CA2203745A1 (fr)	1998-01-26

Family

ID=21801816

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002203745A Abandoned CA2203745A1 (fr)	1996-07-26	1997-04-25	Enzyme de conversion pro-proteinique

Country Status (2)

Country	Link
US (1)	US6380171B1 (fr)
CA (1)	CA2203745A1 (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AUPR673001A0 (en) *	2001-07-31	2001-08-23	Prince Henry's Institute Of Medical Research	Pregnancy-related enzyme activity
TWI353991B (en)	2003-05-06	2011-12-11	Syntonix Pharmaceuticals Inc	Immunoglobulin chimeric monomer-dimer hybrids
WO2007030937A2 (fr) *	2005-09-16	2007-03-22	Institut De Recherches Cliniques De Montreal/I.R.C.M.	Proteines chimeres, lignees cellulaires comprenant celles-ci et dosages pour cribler des modulateurs de proteinase utilisant ces lignees cellulaires
HRP20160990T1 (hr) *	2006-03-24	2016-10-07	Biogen Hemophilia Inc.	Pc5 kao enzim obrade faktor ix propeptida
HRP20191305T1 (hr)	2010-07-09	2019-10-18	Bioverativ Therapeutics Inc.	Preradive jednolančane molekule i polipeptidi izrađeni koristeći iste
EP3508573A1 (fr)	2010-07-09	2019-07-10	Bioverativ Therapeutics Inc.	Systèmes de traitement de facteur viii et procédés associés
EP2863940A4 (fr)	2012-06-08	2016-08-10	Biogen Ma Inc	Facteurs de coagulation chimériques
AU2013270682A1 (en)	2012-06-08	2014-12-11	Biogen Ma Inc.	Procoagulant compounds
TWI828269B (zh)	2013-03-15	2024-01-01	美商百歐維拉提夫治療公司	因子ix多肽調配物
MA40835A (fr)	2014-10-23	2017-08-29	Biogen Ma Inc	Anticorps anti-gpiib/iiia et leurs utilisations
MA40861A (fr)	2014-10-31	2017-09-05	Biogen Ma Inc	Anticorps anti-glycoprotéines iib/iiia

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1994015945A1 (fr)	1992-12-31	1994-07-21	Texas Biotechnology Corporation	Molecules antisens dirigees contre une famille de genes codant un recepteur du facteur de croissance de fibroblastes
US5866351A (en) *	1993-07-07	1999-02-02	University Technology Corporation	CD4+ T-lymphocyte proteases and genes encoding said proteases

1997
- 1997-04-25 CA CA002203745A patent/CA2203745A1/fr not_active Abandoned
- 1997-07-25 US US09/214,555 patent/US6380171B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
US6380171B1 (en)	2002-04-30

Legal Events

Date	Code	Title	Description
2001-04-25	FZDE	Discontinued

Publication	Publication Date	Title
Rinderknecht	1993	Pancreatic secretory enzymes
Clements	1994	The human kallikrein gene family: a diversity of expression and function
Gilpin et al.	1998	A novel, secreted form of human ADAM 12 (meltrin α) provokes myogenesis in vivo
Bloomquist et al.	1991	Prohormone-converting enzymes: regulation and evaluation of function using antisense RNA
Salamonsen et al.	2003	Complex regulation of decidualization: a role for cytokines and proteases—a review
CA2184908C (fr)	2002-07-02	Cathepsine derivee d'osteoclaste humain
Klemm et al.	1991	Acrosin, the peculiar sperm-specific serine protease
US20050287546A1 (en)	2005-12-29	Novel proteases
EP2339020B1 (fr)	2017-03-08	Méthode de Diagnostique basée sur Proteine plasmatique A associée a la grossesse (PAPP-A).
Yan et al.	1995	A 25.7× 103 M r hydra metalloproteinase (HMP1), a member of the astacin family, localizes to the extracellular matrix of Hydra vulgaris in a head-specific manner and has a developmental function
US6380171B1 (en)	2002-04-30	Pro-protein converting enzyme
Wu et al.	2005	Serine proteases and cardiac function
Reudelhuber et al.	1994	Proteolytic processing of human prorenin in renal and non-renal tissues
Wu	2003	Type II transmembrane serine proteases
Seidah et al.	1992	The cDNA sequence of the human pro-hormone and pro-protein convertase PC1
Matsui et al.	2000	Expression of gelatinases A and B in the ovary of the medaka fish Oryzias latipes
JP4488140B2 (ja)	2010-06-23	セリンプロテアーゼであるコリン
Simmer et al.	2011	Expression of kallikrein‐related peptidase 4 in dental and non‐dental tissues
US6566116B1 (en)	2003-05-20	Matrix metalloprotease
AU712917B2 (en)	1999-11-18	Human glandular kallikrein-1 (hK2)
EP0920494A2 (fr)	1999-06-09	Enzyme de conversion de preproteines
Matsui et al.	2000	Cloning and characterization of mouse Klk27, a novel tissue kallikrein expressed in testicular Leydig cells and exhibiting chymotrypsin‐like specificity
CA2259129A1 (fr)	1998-02-05	Enzyme de conversion de preproteines
Cawley et al.	1996	Immunological identification and localization of yeast aspartic protease 3-like prohormone-processing enzymes in mammalian brain and pituitary
US6977170B2 (en)	2005-12-20	Isolated human hepsin/46 proteins, nucleic acid molecules encoding human hepsin/46 proteins, and uses thereof